Temperature-Switch-Controlled Second Harmonic Mode Sensor for Brain-Tissue Detection.

Identifying brain-tissue types holds significant research value in the biomedical field of non-contact brain-tissue measurement applications. In this paper, a layered metastructure is proposed, and the second harmonic generation (SHG) in a multilayer metastructure is derived using the transfer matrix method. With the SHG conversion efficiency (CE) as the measurement signal, the refractive index ranges that can be distinguished are 1.23~1.31 refractive index unit (RIU) and 1.38~1.44 RIU, with sensitivities of 0.8597 RIU-1 and 1.2967 RIU-1, respectively. It can distinguish various brain tissues, including gray matter, white matter, and low-grade glioma, achieving the function of a second harmonic mode sensor (SHMS). Furthermore, temperature has a significant impact on the SHG CE, which can be used to define the switch signal indicating whether the SHMS is functioning properly. When the temperature range is 291.4~307.9 Kelvin (K), the temperature switch is in the "open" state, and the optimal SHG CE is higher than 0.298%, indicating that the SHMS is in the working state. For other temperature ranges, the SHG CE will decrease significantly, indicating that the temperature switch is in the "off" state, and the SHMS is not working. By stimulating temperature and using the response of SHG CE, the temperature-switch function is achieved, providing a new approach for temperature-controlled second harmonic detection.

What dominates the changeable pharmacokinetics of natural sesquiterpene lactones and diterpene lactones: a review focusing on absorption and metabolism.

Sesquiterpene lactones (STLs) and diterpene lactones (DTLs) are two groups of common phytochemicals with similar structures. It's frequently reported that both exhibit changeable pharmacokinetics (PK) in vivo, especially the unstable absorption and extensive metabolism. However, the recognition of their PK characteristics is still scattered. In this review, representative STLs (atractylenolides, alantolactone, costunolide, artemisinin, etc.) and DTLs (ginkgolides, andrographolide, diosbulbins, triptolide, etc.) as typical cases are discussed in detail. We show how the differences of treatment regimens and subjects alter the PK of STLs and DTLs, with emphasis on the effects from absorption and metabolism. These compounds tend to be quite permeable in intestinal epithelium, but gastrointestinal pH and efflux transporters (represented by P-glycoprotein) have great impact and result in the unstable absorption. As the only characteristic functional moiety, the metabolic behavior of lactone ring is not dominant. The α, ß-unsaturated lactone moiety has the strongest metabolic activity. While with the increase of low-activity saturated lactone moieties, the metabolism is led by other groups more easily. The phase I (oxidation, reduction and hydrolysis reaction) and II metabolism (conjugation reaction) are both extensive. CYP450s, mainly CYP3A4, are largely involved in biotransformation. However, only UGTs (UGT1A3, UGT1A4, UGT2B4 and UGT2B7) has been mentioned in studies about phase II metabolic enzymes. Our work offers a beneficial reference for promoting the safety evaluation and maximizing the utilization of STLs and DTLs.

X4-Tropic Latent HIV-1 Is Enriched in Peripheral Follicular Helper T Cells and Is Correlated with Disease Progression.

Follicular helper T (TFH) cells have been shown to support productive human immunodeficiency virus type 1 (HIV-1) replication and to serve as a key component of the latent viral reservoir. However, the viral characteristics of this latent reservoir and the clinical relevance of this reservoir remain unclear. In this study, we assessed the tropic composition of latent viruses from peripheral TFH (pTFH), non-TFH memory, and naive CD4+ T cells from individuals with HIV-1 infections on suppressive combined antiretroviral therapy (cART). X4-tropic latent HIV-1 was preferentially enriched in pTFH cells compared to levels in the other two subsets. Interestingly, the ratio of X4-tropic latent HIV-1 in pTFH cells not only was robustly and inversely correlated with blood CD4+ T cell counts across patients but also was prognostic of CD4+ T cell recovery in individuals on long-term cART. Moreover, patients with higher X4-tropic latent HIV-1 ratios in pTFH cells showed greater risks of opportunistic coinfections. These findings reveal the characteristics of latent HIV-1 in TFH cells and suggest that the ratio of X4-tropic latent HIV-1 in pTFH cells is a valuable indicator for disease progression and cART efficacy.IMPORTANCE TFH cells have been shown to harbor a significant amount of latent HIV-1; however, the viral characteristics of this reservoir and its clinical relevance remain largely unknown. In this study, we demonstrate that X4-tropic latent HIV-1 is preferentially enriched in pTFH cells, which also accurately reflects the viral tropism shift. The ratio of X4-tropic proviruses in pTFH cells but not in other memory CD4+ T cell subsets is inversely and closely correlated with blood CD4+ T cell counts and CD4+ T cell recovery rates with cART. Our data suggest that the ratio of X4-tropic provirus in peripheral TFH cells can be easily measured and reflects disease progression and treatment outcomes during cART.

Quality assessment and differentiation of Aucklandiae Radix and Vladimiriae Radix based on GC-MS fingerprint and chemometrics analysis: basis for clinical application.

Vladimiriae Radix, a geo-authentic medicinal herb found in Sichuan Province in China, is highly similar in chemical composition and pharmacological activity to Aucklandiae Radix. It is often used in local practice and as a substitute for Aucklandiae Radix in the treatment of gastrointestinal tract diseases. However, Vladimiriae Radix is preferred to Aucklandiae Radix in traditional Chinese medicine in Sichuan. In order to compare the difference in quality between the two species and differentiate them according to their chemical profiles, and further to explain the rationality of using Vladimiriae Radix as a substitute and explore the reason for the medication preference in Sichuan, similarity was evaluated using gas chromatography-mass spectrometry (GC-MS) fingerprinting and chemometric analysis. Volatile compounds were identified by comparing mass spectra with spectral data from the National Institute of Standards and Technology library 14.L (NIST 14.L) and the linear retention indices (RI) with those previously reported. The results showed that the similarity between the samples from Aucklandiae Radix (>96%) was greater than that of Vladimiriae Radix (>80%). In addition, 41 and 38 compounds were identified in 10 batches of Vladimiriae Radix and Aucklandiae Radix, respectively, and 21 compounds were common to both species, of which dehydrocostus lactone and aplotaxene were abundant in both. However, γ-patchoulene, longicyclene, ß-gurjunene, humulene1,2-epoxide, and ß-patchoulene were unique to Vladimiriae Radix, while 4-terpineol, α-ionone, trans-α-bergamotene, γ-selinene, and camphene were characteristic compounds of Aucklandiae Radix. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) suggested that the two species were well differentiated with regard to the level of essential oils. Orthogonal partial least squares discriminant analysis (OPLS-DA) further showed that compounds including costol, aplotaxene, caryophyllene, humulene, and ß-eudesmol, together with the characteristic compounds of the two species, could be regarded as potential markers for differentiation, among which ß-eudesmol, which is richer in Vladimiriae Radix, and ß-patchoulene, which is unique to Vladimiriae Radix, have potential therapeutic effects on gastrointestinal diseases. The results obtained in this study distinguished Vladimiriae Radix and Aucklandiae Radix on a chemical level, and the similarity in chemical constituents may provide a basis for the rationality of Vladimiriae Radix as a substitute, while ß-patchoulene and ß-eudesmol existing in Vladimiriae Radix provide a theoretical basis for its preferential use in Sichuan. The analysis method established here has important implications for the quality control and differentiation of Vladimiriae Radix and Aucklandiae Radix, which can also serve as a reference for the identification of similar species. Graphical abstract.

Adapted nano-carriers for gastrointestinal defense components: surface strategies and challenges.

Nano-carriers (NCs) provide drugs with protective and oriented strategies. Despite their success in parenteral administration, NCs still need to be optimized to meet the more serious obstacles encountered in the gastrointestinal tract (GIT). The main defense mechanisms include renewing mucus, epithelial obstacles and digestion by GIT segments. These hurdles pose challenges even before NCs target molecules or proteins, which has often led to unsatisfactory delivery efficiency. Therefore, a critical focus is the exemption from negative effects of GIT. A series of adapted NCs have been designed based on surface strategies to form an expected distribution and increase gastrointestinal utilization. In this paper, we review the strategies and efforts of NCs to adapt to gastrointestinal defense components, including the mucus, epithelium and gastrointestinal segments; the related gastrointestinal mechanisms and functions are also summarized synchronously. Last, we discuss the delivery challenges in terms of physiopathological GIT and surface properties of the NCs.

[Research status of Periplaneta americana with analyses and prospects of key issues].

Periplaneta americana is one of the common traditional Chinese medicines, which has a long application history. It can tonify spleen, promote blood circulation, induce diuresis to alleviate edema, and promote granulation. It is clinically used for the treatment of alimentary canal diseases, chronic heart failure, cutaneous lesion, periodontitis and other diseases. There are some representative prescriptions, such as Kangfu Xinye, Xinmailong injection, Ganlong capsule, and Xiaozheng Yigan tablet. This paper reviewed the chemical components, pharmacological effects and clinical applications of P. americana, firstly summarized standards for the quality control of P. americana, found out and analyzed the key problems in the research. The aim of this paper is to provide the references for the further development and application of P. americana.

Is implementation of the care transitions intervention associated with cost avoidance after hospital discharge?

BACKGROUND: Poorly-executed transitions out of the hospital contribute significant costs to the healthcare system. Several evidence-based interventions can reduce post-discharge utilization. OBJECTIVE: To evaluate the cost avoidance associated with implementation of the Care Transitions Intervention (CTI). DESIGN: A quasi-experimental cohort study using consecutive convenience sampling. PATIENTS: Fee-for-service Medicare beneficiaries hospitalized from 1 January 2009 to 31 May 2011 in six Rhode Island hospitals. INTERVENTION: The CTI is a patient-centered coaching intervention to empower individuals to better manage their health. It begins in-hospital and continues for 30 days, including one home visit and one to two phone calls. MAIN MEASURES: We examined post-discharge total utilization and costs for patients who received coaching (intervention group), who declined or were lost to follow-up (internal control group), and who were eligible, but not approached (external control group), using propensity score matching to control for baseline differences. KEY RESULTS: Compared to matched internal controls (N = 321), the intervention group had significantly lower utilization in the 6 months after discharge and lower mean total health care costs ($14,729 vs. $18,779, P = 0.03). The cost avoided per patient receiving the intervention was $3,752, compared to internal controls. Results for the external control group were similar. Shifting of costs to other utilization types was not observed. CONCLUSIONS: This analysis demonstrates that the CTI generates meaningful cost avoidance for at least 6 months post-hospitalization, and also provides useful metrics to evaluate the impact and cost avoidance of hospital readmission reduction programs.

Corrigendum: Prognostic values and clinical significance of S100 family member's individualized mRNA expression in pancreatic adenocarcinoma.

[This corrects the article DOI: 10.3389/fgene.2021.758725.].

Prognostic Values and Clinical Significance of S100 Family Member's Individualized mRNA Expression in Pancreatic Adenocarcinoma.

Objective: Pancreatic adenocarcinoma (PAAD) is a common malignant tumor worldwide. S100 family (S100s) is wildly involved in regulating the occurrence, development, invasion, metastasis, apoptosis, and drug resistance of many malignant tumors. However, the expression pattern, prognostic value, and oncological role of individual S100s members in PAAD need to be elucidated. Methods: The transcriptional expression levels of S100s were analyzed through the Oncomine and GEPIA, respectively. The protein levels of S100s members in PAAD were studied by Human Protein Atlas. The correlation between S100 mRNA expression and overall survival and tumor stage in PAAD patients was studied by GEPIA. The transcriptional expression correlation and gene mutation rate of S100s members in PAAD patients were explored by cBioPortal. The co-expression networks of S100s are identified using STRING and Gene MANIA to predict their potential functions. The correlation of S100s expression and tumor-infiltrating immune cells was tested by TIMER. Pathway activity and drug target analyzed by GSCALite. Results: 13 S100s members were upregulated in PAAD tissues. 15 S100s members were associated with TP53 mutation. Expression levels of S100A3/A5/A6/A10/A11/A14/A16/B/P/Z were significantly correlated with the pathological stage. Prognosis analysis demonstrated that PAAD patients with low mRNA levels of S100A1/B/Z or high levels of S100A2/A3/A5/A10/A11/A14/A16 had a poor prognosis. Immuno-infiltration analysis showed that the mRNA levels of S100A10/A11/A14/A16 were correlated with the infiltration degree of macrophages in PAAD. Drug sensitivity analysis showed that PAAD expressing high levels of S100A2/A6/A10/A11/A13/A14/A16 maybe resistant to small molecule drugs. Conclusion: This study identifies the clinical significance and biological functions of the S100s in PAAD, which may provide novel insights for the selection of prognostic biomarkers.

Corrigendum: Prognostic Values and Clinical Significance of S100 Family Member's Individualized mRNA Expression in Pancreatic Adenocarcinoma.

[This corrects the article DOI: 10.3389/fgene.2021.758725.].

Antitumor activity and mechanism of costunolide and dehydrocostus lactone: Two natural sesquiterpene lactones from the Asteraceae family.

Costunolide (COS) and dehydrocostus lactone (DEH) are two natural sesquiterpene lactones with potential antitcancer activity against a range of cancer cell types both in vitro and in vivo, particularly for breast cancer and leukemia. There are many researches that have been taken to characterize these pathways and to reveal their anticancer mechanisms of action of COS and DEH. However, while there is a great deal of evidence detailing the effects of COS and DEH on considerable signaling pathways and cellular functions, a global view of their mechanism of action remains elusive. This review systematically summarizes the antitumor activity and mechanism of COS and DEH in the recent reports, and discusses the effect of the key active part (α-methylene-γ-butyrolactone) of COS and DEH against cancer. Moreover, we also discuss the antineoplastic activity of COS and DEH derivatives to improve the cytotoxicity and safety index. We believe this review can provide a systemic reference to develop COS and DEH as anticancer agents.

Comparative study of raw and processed Vladimiriae Radix on pharmacokinetic and anti-acute gastritis effect through anti-oxidation and anti-inflammation.

BACKGROUND: Vladimiriae Radix (VR) is the dry root of Vladimiria souliei (Franch.) Ling or Vladimiria souliei (Franch.) Ling var. cinerea Ling. Costunolide (CO) and dehydrocostus lactone (DE) are the two most effective active ingredients of VR. Raw Vladimiriae radix (rVR) and processed Vladimiriae radix (pVR) are the two most common forms. They have been used for hundreds of years to treat gastritis, gastric ulcer and gastrointestinal pain, but their protective effects on gastric mucosa have been widely considered to be different, and the mechanism is not clear. PURPOSE: A comparative study of in vivo process and efficacy difference of raw and processed Vladimiriae Radix was carried out to explore the treatment mechanism and to provide reference for the rationality of clinical usage. METHODS: In this study, multi-batch rVR and pVR were used to establish the characteristic chromatograms through high performance liquid chromatography (HPLC) to control the qualities of their extracts. A rapid and accurate ultra-high performance liquid chromatography - mass spectrometry (UPLC-MS) method was established and verified, and the concentrations of CO and DE in plasma of rats after oral administration were determined to analyze the pharmacokinetics. The anti-inflammatory and antioxidant activities of ethanol-induced acute gastric mucosa injury (AGMI) in rats were quantitatively analyzed by ELISA and Westernblot methods. RESULTS: Characteristic chromatograms study showed that there were 9 common characteristic peaks between the chromatograms of rVR and pVR, and there was a high level (> 0.90) of the similarity between batches (only one batch less than 0.90). The increased levels of Tmax, T1/2 and MRT were found in rats treated with the pVR. Animal model studies indicated that both the two forms of VR could relieve AGMI, but pVR could more effectively reduce the content of ethanol in blood and lower the levels of TNF-α, IL-6, IL-1ß, NO, iNOS and MDA, and increase the level of SOD. Results of Westernblot proved that pVR also could inhibit the expression of NF-κB p65, IκBα and up-regulate the expression of HO-1 and NRF2 more operatively to protect gastric mucosa through anti-inflammatory and antioxidant stress mechanisms. CONCLUSION: Compared with rVR, pVR has an accelerated absorption in vivo and its effect time was prolonged, and the observed improvement of anti-AGMI effect was achieved through anti-oxidation and anti-inflammation regulation.

Analysis of the similarities and differences between Auclandia and Vladimirae rhizomes by chemical profiling and chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandiae Radix (AR) and Vladimiriae Radix (VR), as traditional Chinese medicine, have been included in many editions of Chinese Pharmacopoeia with similar efficacy such as promoting qi and relieving pain, which are used to treat chest, hypochondriac, abdominal fullness and pain, diarrhea and tenesmus. In most conditions, VR is used to be a substitute of AR or a local habit. However, whether VR could substitute for AR to play a same role in the formulation and clinical applications needs further study. AIM OF THE STUDY: In this study, similarities and differences between AR and VR would be assessed, and possible reasons that may influence the efficacy of the AR and VR would be explained from the perspective of chemical composition. MATERIALS AND METHODS: HPLC-PDA was used to obtain the data of 10 batches of AR and VR, and to establish chemical fingerprint and chemometric analysis. UPLC-ESI-Q-TOF-MS was used to identify the structure of chemical compounds which contributed to the differences between AR and VR. RESULTS: The chemical fingerprint analysis results showed that 20 peaks in common for AR and 26 peaks in common for VR both presented a good similarity (>0.9), and 15 peaks in common for AR and VR also showed a good similarity (>0.9). Nevertheless, chemometric showed AR was distinct from VR and three chemical compounds, which leading to their differences, were identified by UPLC-ESI-Q-TOF-MS. The three chemical compounds were 3ß-acetoxy-11ß-guaia-4 (15),10 (14)-diene-12,6α-olide, 10α,14-epoxy-11ß-guaia-4 (15)-ene-12,6α-olide and costunolide, respectively. CONCLUSION: In general, AR and VR were highly similar, but their differences were deserved to be paid attention to. This research could provide reference for quality control and set a foundation for clinical applications of AR and VR.

Mechanistic evaluation of gastro-protective effects of KangFuXinYe on indomethacin-induced gastric damage in rats.

KangFuXinYe (KFX), the ethanol extract of the dried whole body of Periplaneta americana, is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China. However, its therapeutic effect and mechanism are not yet well understood. Thus, the aim of this study was to investigate the gastro-protective effects of KangFuXinYe (KFX) in indomethacin-induced gastric damage. Rats were randomly divided into six groups as follows: control, treated with indomethacin (35 mg·kg-1), different dosages of KFX (2.57, 5.14 and 10.28 mL·kg-1, respectively) plus indomethacin, and sucralfate (1.71 mL·kg-1) plus indomethacin. After treatment, rat serum, stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly. Rat serum was further used for metabolomics analysis to research possible mechanisms. Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa. Meanwhile, its treatment significantly increased cyclooxygenase-1 (COX-1), prostaglandin E2 (PGE2) and epidermal growth factor (EGF) levels in rat serum and gastric mucosa. Moreover, KFX decreased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels. Nine metabolites were identified which intensities significantly changed in gastric damage rats, including 5-hydroxyindoleacetic acid, indoxylsulfuric acid, indolelactic acid, 4-hydroxyindole, pantothenic acid, isobutyryl carnitine, 3-methyl-2-oxovaleric acid, sphingosine 1-phosphate, and indometacin. These metabolic deviations came to closer to normal levels after KFX intervention. The results indicate that KFX (10.28 mL·kg-1) exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action (regulating tryptophan metabolism, protecting the mitochondria, and adjusting lipid metabolism, and reducing excessive indomethacin).

Early stages of oxidative stress-induced membrane permeabilization: a neutron reflectometry study.

Neutron reflectometry was used to probe in situ the structure of supported lipid bilayers at the solid-liquid interface during the early stages of UV-induced oxidative degradation. Single-component supported lipid bilayers composed of gel phase, dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and fluid phase, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), phospholipids were exposed to low-dose oxidative stress generated by UV light and their structures were examined by neutron reflectometry. An interrupted illumination mode, involving exposures in 15 min increments with 2 h intervals between subsequent exposures, and a continuous mode involving a single 60 (or 90) min exposure period were employed. In both cases, pronounced differences in the structure of the lipid bilayer after exposure were observed. Interrupted exposure led to a substantial decrease in membrane coverage but preserved its total thickness at reduced scattering length densities. These results indicate that the initial phase during UV-induced membrane degradation involves the formation of hydrophilic channels within the membrane. This is consistent with the loss of some lipid molecules we observe and attendant reorganization of residual lipids forming hemimicellar edges of the hydrophilic channels. In contrast, continuous illumination produced a graded interface of continuously varied scattering length density (and hence hydrocarbon density) extending 100-150 A into the liquid phase. Exposure of a DPPC bilayer to UV light in the presence of a reservoir of unfused vesicles showed low net membrane disintegration during oxidative stress, presumably because of surface back-filling from the bulk reservoir. Chemical evidence for membrane degradation was obtained by mass spectrometry and Fourier transform infrared spectroscopy. Further evidence for the formation of hydrophilic channels was furnished by fluorescence microscopy and imaging ellipsometry data.

Comparative oral and intravenous pharmacokinetics of phlorizin in rats having type 2 diabetes and in normal rats based on phase II metabolism.

Phlorizin (PHZ), a type of dihydrochalcone widely found in Rosaceae such as apples, is the first compound discovered as a sodium-glucose cotransporter (SGLT) inhibitor. It has been confirmed to improve the symptoms of diabetes and diabetic complications effectively. Like other flavonoids, the bioavailability challenge of PHZ is the wide phase I and II metabolism in the digestive tract. In this study, we investigated the pharmacokinetics and contribution of phase II metabolism after the oral and intravenous administrations of PHZ in rats having type 2 diabetes (T2D) and in normal rats. The phase II metabolism characteristics of PHZ were investigated by treating plasma samples with ß-glucuronidase/sulfatase. The contribution ratio of phase II metabolism of PHZ ranged from 41.9% to 69.0% after intravenous injection with three doses of PHZ in normal rats. Compared with the observations for normal rats, AUC0-t and Cmax of PHZ significantly increased and T1/2 of PHZ significantly decreased in T2D rats. PHZ was converted into phloretin (PHT) through an enzyme-catalyzed hydrolysis reaction, and PHT was further transformed into conjugates with glycose after both oral and intravenous administrations. Moreover, it was found that the bioavailability of PHZ was about 5% in T2D rats, which was significantly higher than that in normal rats (0%). In conclusion, compared with the observations for normal rats, the pharmacokinetic characteristics of PHZ significantly changed in T2D rats through oral and intravenous administrations. The bioavailability of PHZ significantly increased in T2D rats. Besides, the phase II metabolites of PHT were the major existing forms in blood after oral and intravenous administrations. Our results indicated that the phase II metabolism characteristics of PHZ should be considered when PHZ is applied for the treatment of diabetes as a drug or functional food.

CD161+ CD4+ T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals.

The presence of an extremely stable latent reservoir of HIV-1 is the major obstacle to eradication, despite effective antiretroviral therapy (ART). Recent studies have shown that clonal expansion of latently infected cells without viral reactivation is an important phenomenon that maintains the long-term stability of the reservoir, yet its underlying mechanism remains unclear. Here we report that a subset of CD4+ T cells, characterized by CD161 expression on the surface, is highly permissive for HIV-1 infection. These cells possess a significantly higher survival and proliferative capacity than their CD161-negative counterparts. More importantly, we found that these cells harbor HIV-1 DNA and replication-competent latent viruses at a significantly higher frequency. By using massive single-genome proviral sequencing from ART-suppressed individuals, we confirm that CD161+ CD4+ T cells contain remarkably more identical proviral sequences, indicating clonal expansion of the viral genome in these cells. Taking the results together, our study identifies infected CD161+ CD4+ T cells to be a critical force driving the clonal expansion of the HIV-1 latent reservoir, providing a novel mechanism for the long-term stability of HIV-1 latency.IMPORTANCE The latent reservoir continues to be the major obstacle to curing HIV-1 infection. The clonal expansion of latently infected cells adds another layer maintaining the long-term stability of the reservoir, but its mechanism remains unclear. Here, we report that CD161+ CD4+ T cells serve as an important compartment of the HIV-1 latent reservoir and contain a significant amount of clonally expanded proviruses. In our study, we describe a feasible strategy that may reduce the size of the latent reservoir to a certain extent by counterbalancing the repopulation and dissemination of latently infected cells.

Medicare Advantage enrollees' use of nursing homes: trends and nursing home characteristics.

OBJECTIVES: To examine temporal trends in the prevalence of nursing home (NH) patients participating in Medicare Advantage (MA) and to identify the characteristics of both these patients and the NHs that provide care for them. STUDY DESIGN: Retrospective cohort study. METHODS: Data sources included the Medicare enrollment file, Minimum Data Set, and facility-level data from the Certification and Survey Provider Enhanced Reporting system. Longitudinal trends of NH use by MA enrollees were examined over the period 2000 to 2013 and logistic regression models were used to identify facility characteristics associated with having a high proportion of MA patients. RESULTS: The proportion of MA enrollees in NHs more than doubled between 2000 and 2013, increasing 125% during this period. Notable differences in facility characteristics were found between NHs that serve high proportions of MA enrollees and other NHs. High-MA NHs tended to be larger facilities affiliated with chains. These NHs also had better quality indicators, such as higher staffing levels, lower use of antipsychotics, and lower odds of rehospitalization. Additionally, high-MA NHs were more likely to be in counties with higher Medicare managed care penetration and less market concentration. CONCLUSIONS: MA plans may be selectively contracting with NHs, as evidenced by the larger shares of MA patients who have been placed in facilities with better performance on quality measures. This may reflect MA plans concentrating enrollees in specific facilities and building "networks" of postacute and long-term care providers that provide better and more efficient care.

Medicare Advantage Ratings And Voluntary Disenrollment Among Patients With End-Stage Renal Disease.

Populations with intensive health care needs and high care costs may be attracted to insurance plans that have high quality ratings, but patients may be likely to disenroll from a plan if their care needs are not met. We assessed the association between publicly reported Medicare Advantage plan star ratings and voluntary disenrollment of incident dialysis patients in the following year over the period 2007-13. We found that Medicare Advantage (MA) plans with lower star ratings had significantly higher rates of disenrollment by incident dialysis patients in the following year. Compared to MA plans with 4.0 or more stars, adjusted disenrollment rates were 3.9 percentage points higher for plans with 3.5 stars, 5.0 percentage points higher for those with 3.0 stars, and 12.1 percentage points higher for those with 2.5 or fewer stars. These findings suggest that low plan quality may lead to increased expenditures, as this high-cost population generally must shift from Medicare Advantage to traditional Medicare upon disenrollment.

Regional Variations: The Use Of Hospitals, Home Health, And Skilled Nursing In Traditional Medicare And Medicare Advantage.

In the traditional Medicare program, the use of health care services-particularly postacute care-varies substantially across geographic regions. Less is known about such variations in Medicare Advantage (MA), which is growing rapidly. Insurers that are paid on a risk basis, as in MA, may have incentives and tools to restrain the use of services, which could attenuate geographic variations. In this study of fifty-four million Medicare beneficiaries in the period 2007-13, we found that geographic variations in the use of skilled nursing facility and hospital care in the MA population exceeded those in traditional Medicare, though variations in the use of home health care were greater in traditional Medicare. Within hospital referral regions, the correlations between the use of services in MA and traditional Medicare were moderate to strong. The findings suggest that regional variations in hospital and postacute care reflect local factors that influence beneficiaries' use of services irrespective of the way they obtain coverage.